Respiratory System: Gas Exchange and Functions

• Respiration
  • Ventilation of the lungs (breathing)
  • Exchange of gases between the air and blood, and between blood and the tissue fluid
  • The use of oxygen in cellular metabolism
• Focus on respiration as the exchange of gases between air and blood, and between blood and the tissue fluid for this course.
• Definition of arteries and veins is not based on oxygen content
• Functions of the respiratory system include:
  • O2 and CO2 exchange between blood and air
  • Speech and other vocalizations
  • Sense of smell
  • Affecting pH of body fluids by eliminating CO2
  • Affecting blood pressure by synthesis of vasoconstrictor, angiotensin II
  • Breathing creates pressure gradients between thorax and abdomen to promote lymph and venous blood flow
  • Breath-holding helps expel abdominal contents during urination, defecation and childbirth (Valsalva maneuver)

Conducting Division

• Passages that serve only for airflow
• No gas exchange
• Nostrils through major bronchioles

Respiratory Division

• Consists of alveoli and other gas exchange regions
• Functions of the nose
  • Warms, cleanses, and humidifies inhaled air
  • Detects odors in the airstream
  • Serves as a resonating chamber to amplify the voice
• Functions of the larynx
  • Voice box, cartilaginous chamber
  • Keeps food and drink out of the airway
  • Evolved into phonation (production of sound)
• Histology of the trachea
  • Inner lining: ciliated pseudostratified columnar epithelium
  • Mucus-secreting cells, ciliated cells and stem cells
  • Mucociliary escalator mechanism for debris removal
  • Mucus traps inhaled particles
  • Upward beating cilia drives mucus toward pharynx where it is swallowed
  • Middle layer: connective tissue beneath the tracheal epithelium
  • Lymphatic nodules, mucous serous glands, and tracheal cartilages
• Anatomical Features of Lungs:
  • R lung: shorter than L because the liver rises high on the right
  • Has 3 lobes: superior, middle, and inferior, separated by horizontal and oblique fissure
  • L lung: taller and narrower because the heart tilts toward the left
  • Indentation: cardiac impression
  • Has 2 lobes: superior and inferior separated by a single oblique fissure
• Bronchial Tree Sequence: bronchi - bronchioles – terminal bronchioles – respiratory bronchioles
• All divisions of bronchial tree have a large amount of elastic connective tissue
  • Contributes to the recoil that expels air from lungs (passive process)
• Anatomy of the bronchial tree
  • Bronchi have cartilage, mucous glands, and cilia
  • Bronchioles have no cartilage but do have mucous-producing cells and cilia
  • Terminal bronchioles have cilia only, ending the conducting division
  • Respiratory bronchioles have none of the above structures and start the respiratory division
• Functions of cells present in alveoli
  • Type I alveolar cells (or squamous alveolar cells)
    • Thin, broad cells that allow for rapid gas diffusion between alveolus and bloodstream
    • Cover 95% of alveolus surface area
  • Type II alveolar cells (or great alveolar cells)
    • Repair the alveolar epithelium when type I cells are damaged
    • Secrete pulmonary surfactant to prevents alveoli from collapsing during exhalation
  • Alveolar macrophages (or dust cells)
    • Keep alveoli free from debris by phagocytizing dust particles
• Respiratory membrane is the barrier between the alveolar air and blood, consisting of squamous alveolar cells, endothelial cells of blood capillary, and their shared basement membrane

Pleura

• Visceral pleura – serous membrane that covers lungs
• Parietal pleura – adheres to mediastinum, inner surface of the rib cage and superior surface of the diaphragm
• Pleural cavity – potential space between pleurae
• Normally no room between membranes, but contains a film of slippery pleural fluid
• Functions of pleura: reduce friction, create pressure gradient, and compartmentalization (prevents spread of infection)

Pulmonary Ventilation

• Breathing (pulmonary ventilation) consists of a repetitive cycle: one cycle of inspiration (inhaling) and expiration (exhaling)
• Muscles of respiration:
  • Diaphragm: prime mover of respiration
  • Internal and external intercostal muscles: stiffens thoracic cage during respiration & prevents from caving in
  • Scalenes: quiet respiration, holds ribs 1 and 2 stationary
• Brainstem centers that control breathing
  • Neurons in medulla oblongata and pons control unconscious breathing
  • Voluntary control by motor cortex
• Specific functions of respiratory groups located in medulla oblongata
  • Ventral respiratory group (VRG) is the primary generator of the respiratory system
  • Dorsal respiratory group (DRG) modifies the rate and depth of breathing and receives influences from external sources, such as chemoreceptors
• The pontine respiratory group (located in pons) modifies the rhythm of the VRG by outputs to both the VRG and DRG
• Adapts breathing to special circumstances such as sleep, exercise, vocalization and emotional responses
• Central chemoreceptors are brainstem neurons that respond to changes in pH of cerebrospinal fluid
• Peripheral chemoreceptors respond to pH of blood and O2 and CO2 content, and are located in carotid and aortic bodies of the large arteries above the heart
• Irritant receptors are nerve endings amid the epithelial cells of the airway that respond to smoke, dust, pollen, chemical fumes, cold air, and excess mucus
• Trigger protective reflexes like shallow breathing or coughing
• Stretch receptors:
  • Found in the smooth muscles of bronchi and bronchioles, and in the visceral pleura
  • Respond to inflation of the lungs
• Inflation (Hering-Breuer) reflex: triggered by excessive inflation
• Hyperventilation: anxiety-triggered state in which breathing is so rapid that it expels CO2 from the body faster than it is produced
• Reduced cerebral perfusion from cerebral arteries constricting
• Pressure, Resistance, and Airflow:
  • Flow of a fluid is directly proportional to the pressure difference between two points
  • Inversely proportional to the resistance
  • Atmospheric pressure drives respiration
• Boyle's Law: At a constant temperature, the pressure of a given quantity of gas is inversely proportional to its volume
• Charles' Law: The given quantity of a gas is directly proportional to its absolute temperature
• Pneumothorax: presence of air in pleural cavity
  • Thoracic wall is punctured, lungs recoil and collapse
• Factors That Affect Resistance To Airflow:
  • Diameter of the bronchioles
    • Epinephrine and sympathetic nervous system cause bronchodilation, increasing airflow
    • Histamine, parasympathetic nervous system, cold air, and chemical irritants cause bronchoconstriction, decreasing airflow
    • Extreme bronchoconstriction by anaphylactic shock and asthma can cause suffocation
• Pulmonary compliance
• The ease with which the lungs can expand
• Reduces pulmonary compliance
• Reduced by degenerative lung diseases in which the lungs are stiffened by scar tissue
• Surface tension of the alveoli and distal bronchioles
  • Pulmonary surfactant produced by great alveolar cells (type II cells) reducing surface tension of water
• IRDS = infant respiratory distress syndrome = lack of surfactant

Alveolar Ventilation

• Anatomical dead space: conducting division of airway where there is no gas exchange
• Can be altered somewhat by sympathetic and parasympathetic stimulation
• Pathological dead space: some alveoli may be unable to exchange gases because they lack blood flow, or the respiratory membrane has been thickened by edema or fibrosis
• Physiological (total) dead space: sum of anatomical and any pathological alveolar dead space
• Alveolar ventilation rate (AVR): air that ventilates alveoli (350 mL) X respiratory rate (12 bpm) = 4,200 mL/min
• Most directly relevant to the body's ability to get oxygen to the tissues and dispose of carbon dioxide
• Spirometer: recaptures expired breath and records such variables as rate and depth of breathing, speed of expiration, and rate of oxygen consumption
• Respiratory Volumes and Capacities:
  • Total lung capacity = TV + IRV + EVR + RV
  • Tidal volume: volume of air inhaled and exhaled in one cycle during quiet breathing (500 mL)
  • Inspiratory reserve volume: air in excess of tidal volume that can be inhaled with maximum effort (3,000 mL)
  • Expiratory reserve volume: air in excess of tidal volume that can be exhaled with maximum effort (1,200 mL)
  • Residual volume: 1,300 mL that cannot be exhaled with max effort
  • Vital capacity: tidal + inspiratory + expiratory volumes
  • Forced expiratory volume
• Restrictive disorders: those that reduce pulmonary compliance which limits the amount to which the lungs can be inflated
  • Pulmonary fibrosis -Black lung disease
  • Tuberculosis
  • Show in spirometry as a reduced vital capacity
• Obstructive disorders: interfere with airflow by narrowing or blocking the airway
  • Asthma, chronic bronchitis, and emphysema interferes to inhale/exhale
  • Reduced forced expiratory volume occurs
  • Healthy adult should be able to expel 75% to 85% of the vital capacity in 1 second
• Types of respiratory rhythm:
  • Eupnea: relaxed, quiet breathing, tidal volume 500 mL and the respiratory rate of 12 to 15 bpm
  • Apnea: temporary cessation of breathing (Ex. Sleep apnea)
  • Dyspnea: labored, gasping breathing; shortness of breath (Ex. Congestive heart failure)
  • Hyperpnea: increased rate and depth of breathing in response to exercise, pain or other conditions -Hyperventilation: increased pulmonary ventilation in excess of metabolic demand

Gas Exchange and Transport

• Partial pressure: the separate contribution of each gas in a mixture
  • At sea level 1 atm of pressure = 760 mmHg
  • Movement of gases (O2 and CO2) from alveoli to blood and from blood to alveoli is a result of differences in PARTIAL pressures of individual gases
• Dalton's law: the total atmospheric pressure is the sum of the contribution of the individual gases
  • Air movement INTO and OUT of the lungs is a result of a difference in a TOTAL air pressure
  • Alveolar air has more CO2, more H20, and less O2 that inspired air
  • Air is humidified through mucous membranes
  • Freshly inspired air mixes with residual air left from previous respiratory cycle
  • Alveolar air exchanges O2 and CO2 with the blood
• Alveolar gas exchange
  • The back-and-forth traffic of O2 and CO2 across the respiratory membrane
• Henry's law:
  • At the air-water interface, for a given temperature, the amount of gas that dissolves in the water is determined by its solubility in water and its partial pressure in air
  • Gases diffuse down their own concentration gradient until the partial pressure of each gas in the air is equal to its partial pressure in water
  • The greater the PO2 in the alveolar air, the more 02 the blood picks up
  • Partial pressures of all gases are lower, less O2 diffuses into the blood
• Hyperbaric oxygen therapy treats with O2 at greater than 1 atm of pressure
• Membrane surface area = 100 mL blood in alveolar capillaries, spread thinly over 70m^2
  • Emphysema, lung cancer and tuberculosis decrease surface area for gas exchange
  • Membrane thickness is only .5 um thick which presents little obstacle to diffusion
• Pulmonary edema is L ventricular failure causes edema and thickening of the respiratory membrane
• Pneumonia causes thickening of respiratory membrane
• Distance to travel between blood and air
• Ventilation-perfusion coupling: the ability to match ventilation and perfusion to each other
  • Gas exchange requires both good ventilation of alveolus and good perfusion of the capillaries
  • Ventilation – perfusion ratio of .8: a flow of 4.2 L of air and 5.5 L of blood per minute
  • Ventilation matches perfusion, perfusion matches ventilation
• Gas Transport: the process of carrying gases from the alveoli to the systemic tissues and vice versa
  • Oxygen transport:
  • 98.5% bound to hemoglobin
  • 1.5% dissolved in plasma
  • Carbon dioxide transport:
    • 90% as bicarbonate ion
    • 5% bound to hemoglobin
    • 5% dissolved in plasma
• Hemoglobin: molecule specialized in oxygen transport
  • Oxyhemoglobin (HbO2) – O2 bound to hemoglobin
  • Deoxyhemoglobin (HHb) – hemoglobin with no O2
  • 100% saturated Hb with 4 O2 molecules in alveoli
  • 50% saturation Hb with 2 O2 molecule
• Carbon monoxide (CO)
  • Competes for the O2 binding sites on the hemoglobin molecule (toxic and odorless- odor is added by company supply)
  • Binds to ferrous ion of hemoglobin (Carboxyhemoglobin)
  • Binds 210 times as tightly as oxygen ties up hemoglobin
• Systemic Gas Exchange: the unloading of O2 and loading of CO2 at the systemic capillaries
• Alveolar Gas Exchange Revisited: reaction that occurs in the lungs are reverse of systemic gas exchange
• Hemoglobin unloads o2 to match metabolic needs of difference states of activity of the tissues
• 3 factors that adjust the rate of O2 unloading:
  • Ambient PO2: active tissue has less PO2; O2 is released from Hb
  • Temperature: active tissue has higher temp; promotes O2 unloading. Same in a fever
  • Bohr effect: active tissue has higher CO2, which lowers pH of blood; promoting O2 unloading
• Blood Gases and the Respiratory Rhythm:
  • Rate and depth of breathing adjust to maintain levels of pH, PC02 and P02
  • brainstem respiratory centers receive input from central and peripheral chemoreceptors that monitor the composition of blood and CSF
• Acidosis: blood pH lower than 7.35
• Most common cause is hypercapnia: PC02 greater than 43 mmHg
• Alkalosis: blood pH higher than 7.45
• Most common cause is hypocapnia: PC02 less than 37 mmHg
• pH imbalances resulting from a mismatch between the rate of pulmonary ventilation and the rate of CO2 production
• Metabolic acidosis: body accumulates too much acid in the blood, resulting in a low pH level
• Develop ketoacidosis: by rapid fat oxidation releasing acidic ketone bodies (diabetes mellitus)